Diet-Induced Hyperinsulinemia Accelerates Growth of Androgen-Independent PC-3 Cells In Vitro

Abstract

We investigated the effect of insulin and diet-induced hyperinsulinemia on the growth of the PC-3 cells in vitro and discerned the growth promoting effect of insulin in the androgen-independent cells. Sprague-Dawley rats were kept on a high-fat diet for 4 wk for the induction of insulin resistance and hyperinsulinemia. Insulin alone or serum of the rats kept on either normal-pellet diet or high-fat diet was used to stimulate the serum-starved PC-3 cells growth in culture. S961, a high-affinity insulin-receptor antagonist, was used to confirm the insulin-mediated effects. Significant impairment in the glucose disposal rate and increase in the serum glucose and insulin levels was observed in the high-fat-diet-fed rats. The media supplemented with the serum of the high-fat-diet-fed rats accelerated the growth of the PC-3 cells in comparison to that of normal-pellet-diet-fed rats. Insulin treatment led to accelerated growth of the serum-starved PC-3 cells in a dose-dependent manner and inhibited by the S961 pretreatment. Insulin and serum of the diet-induced hyperinsulinemic rats promote the growth of androgen-independent prostate cancer PC-3 cells. Further, our results provide support for the concept that diet-associated elevation in insulin level may augment the growth of prostate cancer cells.